The long range objectave of this proposal is to investigate lipoprotein synthesis by liver and gut in normolipidemic and various hyperlipidemic states in humans and in hypercholesterolemic rats. (HCR) The Golgi apparatus of liver and small intestine from HCR will be isolated and the nascent lipoproteins retrieved. These uncirculated lipoproteins will be separated into classes and each class will be characterized morphologically, electrophoretically and by lipid composition. The apoproteins of the nascent HCR hepatic and gut lipoprotein will be identified using SDS-polyacrylamide gel electrophoresis and antibodies directed against specific rat serum lipoprotein apoproteins. These data will permit a comparison between nascent HCR liver and gut lipoproteins and HCR circulating plasma lipoproteins as well as comparisons to lipoproteins from normal fed rats. Golgi apparatus from normal human liver and small intestine will also be isolated and the associated lipoproteins characterized as described above. Nascent human liver and gut lipoproteins will be compared to circulating human plasma lipoproteins. These studies will be extended to subjects who have died with various lipid disorders.